GENERAL INTERNAL MEDICINE & HEALTH SERVICES RESEARCH CASE CONFERENCE TEACHING MODULE Hirsutism - Answer key Reviewed by Lisa Skinner, MD July 2011
Articles: #1: Endocrine Society Clinical Practice Guideline #2: A Practical Approach to Hirsutism #3: Evaluation and treatment of Women with Hirsutism (just look at Figure 1, page 2569) #4: Evaluation of Women with Hirsutism (Table 2 only) Susan Silverman is a 22 year old woman without significant past medical history. She presents with a 6-month history of increased body hair. She reports slight increase in hair growth since puberty but has noticed significant increased growth of hair on her face, back and legs for the last 6 months.

She reports that she’s been also feeling depressed lately about how she looks and has been gaining weight over the last year. Another doctor had started her on Prozac recently but she decided not to take it since she thinks her depression is only related to her self-image.

She reports that her periods have always been irregular. Her family history is negative for hirsutism. She is not taking any medications and does not smoke or drink. She does have acne, denies other evidence of endocrinopathy.

2) What is the difference between hirsutism and hypertrichosis? How can you quantify hair growth on physical exam? What are some limitations to this formalized quantification?Hypertrichosis: generalized increase in hair, not in androgen dependent areas and usually hereditary Hirsutism: excessive terminal hairs (darker and thicker) in androgen dependent areas Quantify by Ferriman-Gallwey score (see Article #1, Figure 1) each of 9 body areas rated on amount of hair growth from 1 to 4, a score of over 8 suggests hirsutism. Limited by the subjective nature, the failure to account for focal high score, lack of consideration of certain areas like the sideburns and buttocks, lack of allowance for ethnic variations, and problem of patients employing hair-removal strategies prior to examination.

4) What is in your differential diagnosis? See Article #4, Table 2 Increased peripheral androgen Idiopathic PCOS Hyperthecosis Nonclassical Congenital Adrenal Hyperplasia Neoplasm Ovarian Functional Adrenal Adenoma Carcinoma Cushing’s Drug induced (anabolic steroids, danazol, valproic acid) On exam her bp is 120/75 and she is slightly obese. She has noticeable increased hair growth on her face, chest, lower abdomen and back with moderate acne on her face. A pelvic exam is normal and she has no other evidence of virilizatton.

5) What labs/studies are you going to order as part of your initial evaluation? Guidelines recommend testing for elevated androgens in women with moderate to severe hirsutism OR 1.) sudden onset 2.) rapid progression 3.) menstrual irregularity 4.) central obesity 5.)acanthosis nigricans or 6.) clitoromegaly (virilization). If hirsutism is isolated and mild, no need for laboratory testing and can proceed with treatment. See Article #3, Figure 1 Algorithm. Since she has menstrual irregularities but no virilization, can pursue moderate initial testing: TSH, prolactin, free testosterone and 17-OH progesterone. Can also consider DHEA-S to rule out adrenal cause of androgen production. Endocrine society Guidelines algorithm (Figure 2) recommends simply starting with AM plasma free testosterone as initial evaluation and pursuing additional workup if testosterone is elevated. This may be more cost-effective, but involves more blood draws and appointments for the patient.

A word about testosterone tests: Assays vary, but plasma free testosterone is significantly more sensitive than total testosterone. At UCLA lab, the intial test would be “Testosterone free and total”. There is another test, “Testosterone, bioavailable” which can be sent to a referral lab. This would be useful if the initial evaluation is negative but patient is clinically progressing and you have a high suspicion of an initial false negative for hyperandrogenemia.

Plasma free testosterone is slightly elevated. What are the most likely causes of the patient’s symtoms? Do you want to do any more testing? PCOS is the most likely cause of hyperandrogenic hirsuitism. However, if the testosterone is >200ng per dL, need to rule out ovarian tumor with pelvic ultrasound. If DHEA-S (the adrenal androgen) elevated, should pursue adrenal imaging.

Androgen excess is confirmed on early morning testosterone testing. DHEA-S, TSH, prolactin, and 17-0H progesterone levels are normal. You diagnose Susan with PCOS; however, she remains very concerned about her appearance.

6) What are the pharmacological and non-pharmacological treatments are available? Weight loss is recommended. OCPs Anti-androgens (teratogenic to male fetuses, must use with reliable birth control) Spironolactone-androgen antagonist Finasteride CPA (not available in the USA) Flutamide (GnRH antagonist- not recommended due to modest benefit with significant side effects) Vaniqa (eflornithine hydrochloride) Laser/electrolysis * Metformin has not really been shown to be effective for hirsutism (though likely important for other effects of PCOS)

7) You decide to start her on a birth control pill as first line. What dose of estrogen and what formulation of progesterone are you looking for in the pill that you choose? Theoretically, you want 30-35mcg of estradiol instead of the low dose 20mcg pills, but there is no evidence to support this. Also, theoretically avoid levonorgestrel (most androgenic progestin) and favor drospirenone (anti-androgenic) or norgestimate and desogestrel. Examples: Yaz (drospirenone/ethinyl estradiol) 3mg/20mcg Yasmin/Ocella (drospirenone/ethinyl estradiol) 3mg/30mcg Desogen / Ortho-Cept / Reclipsen (desogestrel/ethinyl estradiol) 0.15mg/30mcgSprintec / Ortho-Cyclen (ethinyl estradiol/norgestimate) 35mcg/0.25mg

Susan returns to clinic after two months of taking the medications you prescribed and reports that her acne is better but the hirsutism is about the same.

How long does hirsutism take to respond to therapy? It may take 9-12 months to show a response to treatment

PROGESTERONE ENZYME IMMUNOASSAY TEST KIT Catalog Number: PS-1113 Enzyme Immunoassay for the PRINCIPLE OF THE TEST Quantitative Determination of Progesterone Concentration in The progesterone EIA is based on the principle of Human Serum competitive binding between progesterone in the test specimen and progesterone-HRP conjugate for a constant amount of rabbit anti-prog